miR-631的表达与卵巢上皮性癌预后的关系

The relationship between expression of miR-631 and prognosis of epithelial ovarian cancer

目的:分析微小RNA-631(miR-631)的表达量与卵巢上皮性癌(EOC)患者临床病理特征和预后的关系,并探讨miR-631对EOC细胞迁移的作用及对成瘤体积的影响。方法:从癌症和肿瘤基因图谱(TCGA)数据库中提取570例EOC患者的临床病理特征及相应的miR-631的相对表达量,由X-tile软件计算出miR-631相对表达量的最佳截断值,根据此最佳截断值将患者分为miR-631高表达组和miR-631低表达组,再用KaplanMeier曲线和COX比例风险模型来评估miR-631表达量在EOC患者中的预后价值。挑选miR-631低表达的EOC细胞株A2780、COV504和miR-631高表达的细胞株ES2和SKOV3,分别上调和下调miR-631表达量,观察细胞迁移能力。建立裸鼠EOC模型,分为对照组和miR-631类似物组,观察2组肿瘤体积。结果:Kaplan-Meier分析显示,miR-631低表达组(miR-631相对表达量<4.78)的EOC患者的总体生存期(OS)较miR-631高表达组(miR-631相对表达量≥4.78)差(HR=0.65,95%CI=0.47~0.89,P=0.008)。单因素和多因素COX回归分析发现miR-631的表达可能是影响EOC患者预后的独立因素(HR=0.72,95%CI=0.54~0.97,P=0.029)。上调miR-631的表达会抑制EOC细胞的迁移,下调miR-631的表达会促进EOC细胞的迁移。在EOC裸鼠模型中,上调miR-631会减小EOC体积。结论:miR-631的低表达可能预示着EOC患者预后较差,上调miR-631可以抑制EOC细胞的迁移,并且可以显著地减小肿瘤体积,可能对EOC有治疗意义。

Objective: To explore the data of epithelial ovarian carcinoma(EOC) patients in the Tumor and Cancer Gene Map(TCGA) database by analyzing the relationship between the expression of microRNA-631(miR-631) and the clinicopathological features and prognosis of EOC patients and to investigate the effect of miR-631 on EOC cell migration and tumor volume. Methods: Clinical pathological features and corresponding microRNA expression date were extracted from TCGA database of 570 patients with EOC. The optimal cutoff value of miR-631 expression was calculated by X-tile software, and based on this optimal cutoff value the patients were grouped. The Kaplan-Meier curve and the Cox proportional hazards model was performed to assess the prognostic value of miR-631 expression in EOC patients. The miR-631 low-expressing EOC cell lines A2780, COV504 and miR-631 high-expressing cell lines ES2 and SKOV3 were selected by up-regulating the expression of miR-631 in low-expressing cell lines and down-regulating the expression in high-expressing cell lines to observe the ability of cell to migrate. The nude mouse EOC model was established and divided as the control group and miR-631 mimic group. The tumor volume of the two groups was observed. Results: KaplanMeier analysis showed that the overall survival(OS) of EOC patients with miR-631 low-level expression group(miR-631 expression value<4.78) was higher than that of EOC patients with miR-631 high-level expression group(miR-631 expression value≥4.78)(HR=0.65, 95%CI=0.47-0.89, P=0.008). Univariate and multivariate COX regression analysis revealed that miR-631 expression may be an independent factor influencing the prognosis of patients with EOC(HR=0.72, 95%CI=0.54-0.97, P=0.029). Up-regulation of miR-631 expression inhibits migration of EOC cells, and down-regulation of miR-631 expression promotes migration of EOC cells. Upregulation of miR-631 expression in the EOC nude mouse model reduced EOC tumor formation volume. Conclusion: Low expression of miR-631 may indicate poor prognosis in patients with EOC. Up-regulation of miR-631 can inhibit EOC migration and significantly reduce tumor volume, which may have therapeutic implications for EOC.